Signal transduction in cancer biology and therapy
Current state of research
Research on cellular signal transduction is highly relevant for the development of new cancer therapies. Related research activities are ongoing within the Jena University Hospital (JUH) but also at the Institute of Biochemistry and Biophysics of the Faculty of Biology and Pharmacy (IBB), and the Leibniz Institute for Age Research, Fritz-Lipmann Institute (FLI). There is a history of collaboration between a number of these research groups often in basic research in the framework of the DFG SFB 604 “Multifunctional Signaling Proteins” (2002-2009). Further interactions, notably between basic research and clinic, shall be fostered in the corresponding section of the CCC by implementing the specific CCC activities of education and training and by providing access to the infrastructural funds.
Coordinators
Institution |
Names |
JUH, Department of Hematology/Oncology |
Thomas Ernst, Andreas Hochhaus, |
JUH, Childrens Hospital |
James Beck, Jürgen Sonnemann |
JUH, Institute of Human Genetics |
Aria Baniahmad |
JUH, Institute of Biochemistry II |
Karlheinz Friedrich, Otmar Huber |
JUH, Clinics of General, Visceral and Vascular Surgery |
Roland Kaufmann, Utz Settmacher |
JUH, Institute of Pharmacology and Toxicology |
Stefan Schulz, Ralf Stumm |
JUH, Institute of Molecular Cell Biology, CMB |
Frank-D. Böhmer, Jörg Müller, |
Jena University, Faculty for Biology and Pharmacy, CMB |
Thorsten Heinzel, Oliver Krämer, |
FLI, Leibniz Institute for Age Research |
Christoph Englert, Cornelis Calkhoven, |
Topics for future joint research
1. Mechanisms of epigenetic regulation and their alterations in cancer
- affecting gene expression
- protein stability, turnover, and localization
2. Novel targets and novel combinations of signal transduction effectors to overcome
- treatment resistance of cancer cells
- persistence of cancer stem cells
Recent Grant Acquisition
Newly awarded grants: 13
Baniahmad, Englert, Ernst, Friedrich, Hochhaus (2), Kaufmann/Settmacher (2),
Krämer (2), Morrison
DFG, Deutsche Krebshilfe, ESH/ASH, BMBF, EU, Sander-Stiftung, Carreras-Stiftung
Submitted grant applications: 4
Baniahmad, Böhmer, Calkhoven, Schönherr/Heinemann
DFG, Deutsche Krebshilfe,
Examples of ongoing cooperative research
Regulation of Androgen Receptor in prostate cancer
Role of WT1, a target of HDAC-inhibitors, in leukemia
Novel mutations in epigenetic genes
Anti-tumor activity of histone-deacetylase inhibitors (HDACi)
Publications
- Hughes T, Saglio G, Branford S, Soverini S, Kim DW, Müller MC, Martinelli G, Cortes J, Beppu L, Gottardi E, Kim D, Erben P, Shou Y, Haque A, Gallagher N, Radich J, Hochhaus A. Impact of baseline BCR-ABL mutations on response to nilotinib in patients with chronic myeloid leukemia in chronic phase. J Clin Oncol. 2009, 27:4204-10.
- Ernst T, Chase AJ, Score J, Hidalgo-Curtis CE, Bryant C, Jones AV, Waghorn K, Zoi K, Ross FM, Reiter A, Hochhaus A, Drexler HG, Duncombe A, Cervantes F, Oscier D, Boultwood J, Grand FH, Cross NC. Inactivating mutations of the histone methyltransferase gene EZH2 in myeloid disorders. Nat Genet. 2010, 42:722-6.
- Schmidt-Arras, D, Böhmer, S.A., Koch, S, Müller, JP, Blei, L, Cornils, H, Bauer, R, Korasikha, S, Thiede, C, Böhmer, FD Anchoring of FLT3 in the endoplasmic reticulum alters signaling quality. Blood 2009, 113: 3568-76.
- Krämer OH, Knauer SK, Greiner G, Jandt E, Reichardt S, Gührs KH, Stauber RH, Böhmer FD and Heinzel T A phosphorylation-acetylation switch regulates STAT1 signaling. Genes & Development 2009, 23, 223-235.
- Müller C, Bremer A, Schreiber S, Eichwald S and Calkhoven CF Nucleolar retention of a translational C/EBPα isoform stimulates rDNA transcription and cell size. EMBO J. 2010, 29, 897-909